All biological constituents of any organism are the result of xe2x80x9ctrade-offsxe2x80x9d of benefits versus disadvantages that have taken place under millions of years of evolutionary pressure. Thus, almost all developmental and metabolic processes that are necessary for the proper function of an organism also have negative side effects that are generally more long term in nature.
The human aging processes themselves now appear to be a result of such trade-offs involving the side reactions of development and energy metabolism. For example, much is known about the harmful side reactions of aerobic metabolism processes in mitochondria, which are very efficient in producing energy. However, free radicals or reactive oxygen species (ROS) are also produced that are toxic by-products of these reactions. If these ROS are not destroyed, they will quickly destroy the cells that produced them.
A compelling body of scientific evidence now indicates that many dysfunctions and diseases in humans are a product of oxidative stress. These include,
Aging: Normal aging processes at a higher than normal rate, Segmental progeria disorders (Down""s syndrome).
Heart and Cardiovascular Disease: Atherosclerosis, Adriamycin cardiotoxicity, Alcohol cardiomyopathy.
Kidney: Autoimmune nephritic syndromes, Heavy metal nephrotoxicity, Solar radiation, Thermal injury, Porphyria.
Gastrointestinal Tract: Inflammatory and immune injury, Diabetes, Pancreatitis, Halogenated hydrocarbon liver injury.
Eye: Cataractogenesis, Degenerative retinal damage, Macular degeneration.
Lung: Lung cancer (cigarette smoke), Emphysema, Oxidant pollutants (03, N02), Bronchopulmonaly dysphasia, Asbestos carcinogenicity.
Nervous System disorders: Hyperbaric oxygen, Parkinson""s disease, Neuronal ceroid lipofuscinoses, Alzheimer""s disease, Muscular dystrophy, Multiple sclerosis.
Red Blood Cells: Malaria, Sickle cell anemia, Fanconi""s anemia, Hemolytic anemia of prematurity.
Iron Overload: Idiopathic hemochromatosis, Dietary overload, Thalassemia
Ischemia Reflow States: Stroke
Inflammatory-Immune Injury: Glomerulonephritis, Autoimmune disease, Rheumatoid Arthritis.
Liver: Alcohol-induced pathology, Alcohol-induced iron overload injury.
Other Oxidative Stress Disorders: AIDS, Radiation-induced injuries (accidental and radiotherapy), General low-grade inflammatory disorders, Organ transplantation, Inflamed rheumatoid joints, Arrhythmias, Myocardial infarction
The general age-dependent decline in optimum health and performance (known as normal aging) appears to be the result of ROS, which is one of its major causative factors. In addition, many different types of bacterial, fungal and viral infections increase the amount of ROS generated in vivo. Sometimes this increase is dramatic (as in AIDS), but it also can be very slight as in a number of low-grade bacterial and fungal infectious diseases.
Basic Concept of Oxidative Stress Profile (OSP) Oxidative stress (OS) is defined as the steady-state level of oxidative damage within a cell, tissue or organism caused by ROS. The degree of oxidative stress or the oxidative stress state (OSS) present in a given biological system is determined by the net result of three major factors. These three factors, identified in FIG. 1, are:
(1) Initial rate of generation of ROS
(2) Level of antioxidant protective processes
(3) Rate of repair and general turnover or removal rate of the oxidized targets that Include nucleic acids, proteins and lipids.
Many of the oxidized damage components that are produced throughout the body are transported to the serum, urine or breath, as denoted by (4) in FIG. 1. The OSS, as denoted by (5) in FIG. 1, can refer to any component or system such as the whole individual, an organ, a tissue, a cell or a subcellular fraction. It is the ratio of damage input, [denoted by (6)], to damage output [denoted by (7)] that determines the OSS value. This ratio is largely controlled by a specific set of genes known as xe2x80x9clongevity determinant genesxe2x80x9d. Diet also offers an effective means of control if it is known what dietary factors are most important and what is best for each individual.
The concept of OSS is fundamental to understanding the health maintenance in humans because it determines the probability that initiation of abnormal functions and diseases will occur over time, as denoted by (8) in FIG. 1. Since initiation and rate of progression with age of major diseases is strongly related to an individual""s characteristic OSS, control of OSS is key to the control of human health and longevity. To achieve this aim, there is a growing need within the scientific and clinical medical communities for (a) specific, reliable, non-invasive and cost-effective assays that are effective in measuring small changes of OSS, and (b) a unique, integrated set of these assays that can be used to calculate most effectively an individual""s OSS.
The invention reported here is given the name, Oxidative Stress Profile (OSP). The OSP provides the most complete set of assays designed to assess the OSS of an individual. These assays are designed for use by (a) the scientific community in basic research, (b) practicing clinicians and medical doctors, and (c) individuals interested in personally optimizing their health and longevity. The OSP is made up of 10 components, each consisting of assays for 2-22 biomarkers of health. These 10 components and the number of biomarkers specific for each component are identified as follows:
1. spot screening (biomarkers #1-7)
2. prooxidant potential (biomarkers #8-14)
3. glycation potential (biomarkers #15-16)
4. total antioxidants (biomarkers #17-20)
5. water-soluble antioxidants (biomarkers #21-24)
6. lipid-soluble antioxidants (biomarkers #25-38)
7. lipids and proteins (biomarkers #3943)
8. cardiac disease risk factors panel (biomarkers #44-50)
9. age-related hormone panel (biomarkers #51-60)
10. mineral and trace element panel (biomarkers #61-82).
Each of the assays used are complimentary with other assays of the profile, thus providing either confirmation information or the synthesis of new information. Thus the diagnostic value of the sum of the assays used in the OSP is much greater than the individual parts. A new technique called the Genox Oxidative Stress Profile Diagnostic Plot (GOSP Diagnostic Plot) has been developed to interpret the assay data from OSP. The GOSP Diagnostic Plot is based on the calculations of two key parameters from an individual OSP.
The first parameter is called the Genox Oxidative Stress Profile Index (GOSPI). It is calculated from 8-10 of the oxidative damage and prooxidant potential assays and represents the average level of oxidative damage with reference to the 100 percent mean level. That is:
GOSPI=1/nxcexa3(Percent of Meanxe2x80x94100%), where n is equal to number of assays in the sum.
The second parameter is called the Genox Antioxidant Profile Index (GAPI). It is calculated from 20-30 of the antioxidant assays and represents the average level of antioxidant protection with reference to the 100 percent mean level. That is:
GAPI=1/nxcexa3(Percent of Meanxe2x80x94100%), where n is equal to number of assays in the sum.
The GOSPI and the GAPI are then plotted on an XY axes to illustrate their relation with reference to about an 300 individuals having similar GOSP Diagnostic Plots. This is shown in FIG. 2.
The diagnostic plot consists of four quadrants, each with noticeable characteristics.
Quadrant I: Individuals in this quadrant have the expected high level of oxidative stress that accompanies low levels of antioxidants. They are therefore expected to respond to higher dosages of antioxidants, as illustrated to lower their OSS.
Quadrant II: Individuals in this quadrant have high OSS levels in spite of above average levels of antioxidant protection. The data obtained from experimental study suggest that this condition is quite common and represents one of the most important applications of the OSP. This condition could develop as a result of stress occurring due to,
(a) High levels of iron and/or copper stress
(b) High levels of inflammatory related disease such as caused by microorganism infections (bacterial, viral low grade infection; examples are AIDS and malaria)
(c) Pharmacological drugs that block antioxidant absorption or synthesis or generate ROS.
(d) Alcoholism
(e) Exposure to toxic environmental factors as trace metals, asbestos.
(f) Oxidative stress related diseases, such as diabetes.
Quadrant III: Individuals in this quadrant have lower than normal OSS, but with a low antioxidant state. This represents an optimal health state, and suggests that even future improvement can be realized through increasing the antioxidant levels. Such cases also indicate that all the relevant antioxidants (most of which are in tissues other than blood) may not be being measured.
Quadrant IV: Individuals in this quadrant have lower than normal OSS, with the expected accompaniment of higher than normal levels of antioxidant protection. Further improvement may be indicated by increasing antioxidants in diet, or possibly lowering endogenous production of antioxidants. What action is best will be indicated by the detail of an individual""s OSP.
In summary, by utilizing the Genox OSP diagnostic plot, along with the specific details of the OSP, the physicians will possess a powerful tool to assist them in the proper treatment of their patients. Since each human is unique as to their heredity, lifestyle and environment exposure, their needs are also unique. The Genox OSP diagnostic plot is a unique tool designed to evaluate the oxidative stress in humans.